The objective of this proposal is to participate in a multicenter collaborative clinical trial to determine whether strict control of blood glucose levels is effective in preventing or ameliorating the vascular complications of insulin-dependent diabetes mellitus. The central hypothesis to be tested is that the degree of altered blood glucose control is an important risk factor in the development and progression of chronic diabetic vascular complcations. Another hypothesis to be tested is that a therapy exists which will restore the metabolic state of the diabetic person to as close to normal as possible and that this therapy can be effectively and safely applied to a large number of individuals over a prolonged period of time. The specific aims of the proposal are to determine if patients treated with an intensive regimen (continuous subcutaneous insulin infusion) can achieve better glucose control than patients treated with a conventional regimen (two daily injections of insulin). In respect to the intensive therapy, we will determine (as part of the multicenter collaborative study) if high rates of patient acceptability are possible and if the treatment is safe. Two treatment groups (intensive vs conventional therapy) will be established and following an extensive baseline evaluation, patients will be monitored at regular intervals for 1) blood glucose control using the results of hemoglobin Alc determinations as well as other means, and for 2) pathologic endpoints such as retinopathy as determined by stereo color trtinal photographs. The study will proceed in three phases, planning of protocols, limited feasibility trial (two years) and if indicated, full scale trial. The proposed studies will provide important new information which will increase our understanding of diabetic vascular complications, and suggest rational approaches to treatment of patients with diabetes mellitus.